Persistent infection of adult mink with the Aleutian mink disease parvovirus (ADV)leads to disturbances of immune regulation, including hypergammaglobulinemia, plasmacytosis, immune complex disease, interstitial and glomerulonephritis. Infection at the cellular level is noncytopathic and restricted. In contrast, infections in cell culture and in newborn mink are cytopathic and fully permissive. Studies in cell culture, using TUNEL labeling and annexin staining, have revealed that cells engaged in permissive ADV infection replication become apoptotic. Pretreatment of cells with a broad-spectrum caspase inhibitor or a specific inhibitor of the executioner caspase 3, blocks permissive replication at a step prior to viral protein expression. Treatment with an inhibitor specific for caspase 6/8 produces a partial block. Thus, ADV induces programmed cell death (apoptosis) and is in fact dependent upon apoptosis for complete viral replication. Populations of native feral mustelids in Spain are declining. The presence of ADV infection has been documented in these animals. More than 1 sequence variant of ADV appears to be circulating and these variants differ from previously identified isolates of ADV.